6g86 | pdb_00006g86

Structure of Cdc14 bound to SIC1 PxL motif

spinqualitylabelsall models 6g86, resolution 1.74Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6g86 is a 4 chain structure with sequence from Atcc 18824. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: MES, P6G, PEG, ZN Gene: CDC14, OAF3, YFR028C (ATCC 18824) Activity: Protein-tyrosine-phosphatase, with EC number 3.1.3.48 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [CDC14_YEAST] Protein phosphatase which antagonizes mitotic cyclin-dependent kinase CDC28, the inactivation of which is essential for exit from mitosis. To access its substrates, is released from nucleolar sequestration during mitosis. Plays an essential in coordinating the nuclear division cycle with cytokinesis through the cytokinesis checkpoint. Involved in chromosome segregation, where it is required for meiosis I spindle dissambly as well as for establishing two consecutive chromosome segregation phases. Allows damaged actomyosin rings to be maintained to facilitate completion of cell division in response to minor perturbation of the cell division machinery. Inhibits transcription of ribosomal genes (rDNA) during anaphase and controls segregation of nucleolus by facilitating condensin targeting to rDNA chromatin in anaphase. Dephosphorylates SIC1, a CDC28 inhibitor, and SWI5, a transcription factor for SIC1, and induces degradation of mitotic cyclins, likely by dephosphorylating the activator of mitotic cyclin degradation, CDH1. Dephosphorylates the microtubule bundling factor ASE1 which is required to define a centered and focused mitotic spindle midzone that can drive continuous spindle elongation. Dephosphorylates the anaphase-promoting complex inhibitor ACM1, leading to its degradation. Facilitates INN1-CYK3 complex formation which promotes cytokinesis through the dephosphosprylation of CDC28-phosphosphorylated INN1. Reverts also the inhibitory CDC28 phosphorylation of CHS2 for endoplasmic reticulum export, ensuring that septum formation is contingent upon chromosome separation and exit from mitosis. Additional substrates for CDC14 are the formins BNI1 and BNR1, as well as CDC6, DBP2, DSN1, INCENP, KAR9, MCM3, ORC2, ORC6, SLD2, and SWI6. Activity is inhibited by interaction with NET1 which sequesters it to the nucleolus. [SIC1_YEAST] Substrate and inhibitor of the cyclin-dependent protein kinase CDC28. Its activity could be important for faithful segregation of chromosomes to daughter cells. It acts in response to a signal from a post-start checkpoint. Publication Abstract from PubMed The cell division cycle consists of a series of temporally ordered events. Cell cycle kinases and phosphatases provide key regulatory input, but how the correct substrate phosphorylation and dephosphorylation timing is achieved is incompletely understood. Here we identify a PxL substrate recognition motif that instructs dephosphorylation by the budding yeast Cdc14 phosphatase during mitotic exit. The PxL motif was prevalent in Cdc14-binding peptides enriched in a phage display screen of native disordered protein regions. PxL motif removal from the Cdc14 substrate Cbk1 delays its dephosphorylation, whereas addition of the motif advances dephosphorylation of otherwise late Cdc14 substrates. Crystal structures of Cdc14 bound to three PxL motif substrate peptides provide a molecular explanation for PxL motif recognition on the phosphatase surface. Our results illustrate the sophistication of phosphatase-substrate interactions and identify them as an important determinant of ordered cell cycle progression. A PxL motif promotes timely cell cycle substrate dephosphorylation by the Cdc14 phosphatase.,Kataria M, Mouilleron S, Seo MH, Corbi-Verge C, Kim PM, Uhlmann F Nat Struct Mol Biol. 2018 Nov 19. pii: 10.1038/s41594-018-0152-3. doi:, 10.1038/s41594-018-0152-3. PMID:30455435 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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